Schmidt, Christoph and Hoecherl, Klaus and Kurt, Birguel and Moritz, Stefan and Kurtz, Armin and Bucher, Michael (2010) Blockade of multiple but not single cytokines abrogates downregulation of angiotensin II type-I receptors and anticipates septic shock. CYTOKINE, 49 (1). pp. 30-38. ISSN 1043-4666,
Full text not available from this repository. (Request a copy)Abstract
In this prospective, randomized animal study, the role of proinflammatory cytokines in the pathogenesis sepsis-induced circulatory failure with downregulation of angiotensin-II-type-I-(AT(1))-receptors was investigated. Sepsis in wild-type mice and in mice with deficiencies for TNF-alpha, IL-1 beta, IFN-gamma or IL-6 was induced by cecal ligation and puncture (CLP) and wild-type mice were injected with cytokines. Animals were treated with glucocorticoids or small interfering RNA (siRNA) targeting single or multiple cytokines or NF-kappa B. Vascular smooth muscle cells (VSMCs) were incubated with cytokines. CLP resulted in circulatory failure and a significant downregulation of AT(1)-receptors. Injection of single proinflammatory cytokines also strongly downregulated AT(1)-receptors paralleled by a markedly endogenous liberation of further cytokines, whereas, simultaneous blockade of these endogenously activated cytokines by dexamethasone prevented downregulation of AT(1)-receptors. Furthermore, inhibition of multiple but not single cytokines by treatment with siRNA against multiple cytokines or NF-kappa B significantly attenuated CLP-induced AT(1)-receptor downregulation and prevented septic circulatory failure. Our data demonstrate that downregulation of AT(1)-receptors during sepsis is due to multiple but not single cytokines and define a relevant role for NF-kappa B in the pathogenesis of septic shock. (C) 2009 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; SYSTEMIC INFLAMMATORY RESPONSE; SMOOTH-MUSCLE-CELLS; GENE-EXPRESSION; SEPSIS; ENDOTOXEMIA; ACTIVATION; RATS; LIPOPOLYSACCHARIDE; VASOPRESSIN; Sepsis; Cytokines; NF-kappa B; Angiotensin II type-I (AT(1))-receptors |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Armin Kurtz |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Aug 2020 06:10 |
| Last Modified: | 17 Aug 2020 06:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25421 |
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